CN101385736A - Use of penoniflorin in preparing medicine for preventing and treating depression and medicine composition thereof - Google Patents
Use of penoniflorin in preparing medicine for preventing and treating depression and medicine composition thereof Download PDFInfo
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Abstract
The invention relates to an application of paeoniflorin in drugs for preventing and treating depression and a pharmaceutical composition thereof, and the pharmaceutical composition contains effective dose of the paeoniflorin and a pharmaceutical acceptable carrier. The pharmaceutical composition can be prepared into various conventional liquid formulations or solid formulations. The paeoniflorin is proved to have better efficacy for the depression and long duration of the efficacy through a rat forced swimming test, a open field test and a new environment feeding inhibition test. The drugs which take the paeoniflorin as an active ingredient and are used for treating and preventing the depression have good effects, long duration, insignificant toxicity and side effect and low price.
Description
Technical field
The present invention relates to the novel medical use and the pharmaceutical composition thereof of peoniflorin.
Background technology
The depression serious harm human life with healthy.Depression (Depression) be meant with depressed, retardation of thinking and with interest lower, the sluggish symptom of degradation psychomotor activity serve as a class mood disorders syndrome that mainly shows under the initiative.Sickness rate is very high, about 15-17%, and be the trend that rises year by year in recent years especially; Estimate that according to World Health Organization (WHO) to the year two thousand twenty, depression will become the first place reason that disables, and be the 21 century mankind's main killer (Murray, 1997).
Peoniflorin (paeoniflorin) is single obedient class glycoside compounds, and its molecular formula is suc as formula shown in the I.Be a kind of natural active matter, come from the root of ranunculaceae plant Radix Paeoniae Paeonia albiflora Pall, the root of Paeonia suffruticosa P.suffrsticosa Andr, the root of Paeonia delavayi P.delarayi Franch, content are high with Radix Paeoniae Rubra.
Present known peoniflorin has multiple medicinal application: paeoniflorin has significant analgesia, anticonvulsant action.The research report is arranged, and (5-100mgkg-1 i.p.) can significantly reduce the pain reaction that Venenum apis causes to paeoniflorin.Antitumor action, peoniflorin can suppress the activity and the rising adenylic acid of ATP enzyme on the tumor cell membrane, the active effect of cyclase (AC).This medicine suppress tumor cell generate, with suppress Na on the film, K-ATPase and to activate AC closely related.Peoniflorin 2mg/ml, 1mg/ml and 0.5mg/ml active drug concentration can suppress the propagation of human liver cancer cell to delay the process of hepatocarcinoma to a certain extent to the prompting peoniflorin.And can induce the HepG2 apoptosis, and energy upregulation of apoptosis related gene P53 and bax expression, downward modulation anti-apoptotic genes expression bcl-2 expresses.Modern pharmacological research shows that peoniflorin also has to be regulated immunity, analgesia, calmness, spasmolytic, blood vessel dilating, antiinflammatory, improves effect such as learning and memory behavior.The peoniflorin intravenous injection can obviously reduce the blood glucose of the diabetic mice that streptozotocin brings out, and sugar content also reduces gradually along with the prolongation of administration time in the blood plasma.Discover that recently peoniflorin also has neuroprotective, but also indeterminate its mechanism of action.Radix Paeoniae is used for the treatment of the dementia disease for a long time, and peoniflorin can alleviate the radial mystery of the rat palace that scopolamine brings out and distinguish obstacle.
The toxicity of peoniflorin is very low, there are some researches show that toxic reaction does not take place the peoniflorin that adds 0.1-1000ug/ml in the normal thymus cell of cultivating; Toxic reaction does not take place in the peoniflorin that adds 160-640ug/ml in U937 cell line (people's myelomonocyte system) yet.
Clinical practice aspect peoniflorin is mainly used in the treatment and the Senile disease of coronary heart disease at present, can make ancillary drug in aspect, the especially treatments of senile chronic respiratory tract disease such as health invigorating and immunologic function, antiinflammatory cough-relieving, eliminating phlegm and relieving asthma.
Summary of the invention
The object of the present invention is to provide the new pharmaceutical usage of peoniflorin, i.e. new application in the medicine of prevention and treatment depression.
The present invention also provides the pharmaceutical composition of a kind of prevention and treatment depression, little, the instant effect, cheap of this pharmaceutical composition toxic and side effects.
The pharmaceutical composition of prevention of the present invention and treatment depression, it comprises the peoniflorin and the pharmaceutically acceptable carrier of effective dose.Described pharmaceutically acceptable carrier is conventional medicine excipient or adjuvant.
Described pharmaceutical composition contains the peoniflorin of 0.1-50% weight.The dosage form of described pharmaceutical composition is liquid dosage form or solid dosage forms.Wherein, described liquid dosage form is injection, solution, suspensoid, Emulsion, aerosol.Described solid dosage forms is tablet, capsule, pill, injectable powder, slow releasing preparation and various particulate delivery system.
Drug effect and pharmacotoxicological effect experiment show: peoniflorin can effectively improve the depressive state of experiment mice.In the forced swimming experimental model, the experiment of mice forced swimming is carried out in peoniflorin abdominal cavity injection continuously after seven days, measures the motionless time of swimming in the 5min.0.5 can both significantly reduce rats'swimming immobility time with 1mg/Kg lumbar injection dosage, on short-term and long-term effect, to compare with matched group, above-mentioned index all has statistically-significant difference, shows that peoniflorin has very strong antidepressant effect.Fluorine Luo Xiting (Fluoxetine) and imipramine (Imizin) are the medicines of the existing treatment depression used always, peoniflorin and these two kinds of medicines contrast, on short run effect, when peoniflorin dosage is 0.5mg/Kg and the non-swimming time there was no significant difference of above-mentioned two kinds of medicines.All there is the statistics notable difference dead time of swimming during for 1mg/Kg when peoniflorin dosage than fluorine Luo Xiting and imipramine; But on long-term effect, particularly found peoniflorin treatment 7 days, detected animal behavior again in 28 days after the drug withdrawal to find that peoniflorin still can shorten the dead time of mice, and effect is better during than 7 days.Fluorine Luo Xiting on the same group can not shorten the dead time of mice, though and imipramine can shorten the dead time of mice, its effect is obviously than 7 day time difference.The antidepressant effect that shows peoniflorin is more lasting, is better than positive control medicine fluorine Luo Xiting and imipramine.
On the unpredictable model of rat chronic, the antidepressant effect that has compared peoniflorin and positive control fluorine Luo Xiting, negative control normal saline in the experiment, found that, compare with normal saline, peoniflorin can improve the spontaneous activity ability of the cleannes of rat, the incubation period (Latency of the noveltysuppressed-feeding test) that shortens rats eating under the new environment, increase rat, these improve similar to fluorine Luo Xiting treatment, illustrate that peoniflorin has antidepressant effect.
The neuron regeneration of hippocampus of growing up has important effect in the generation of depression, evolution, show that on evidence the regeneration of the generation of depression and treatment and adult hippocampal neuron is closely related: at first, nearly all existing antidepressant drug or method are all by the brain neuron that promotes the to grow up antidepressant effect of having regenerated.Secondly, clinical brain imaging technique discovers that the Hippocampus volume of depressive patient obviously dwindles, and along with the improvement of the depressed state of an illness, the volume of Hippocampus can increase gradually.Result of study shows, peoniflorin significantly increases the ventricles of the brain other district Brdu positive cell number, wherein dosage 0.5mg/Kg has compared remarkable significant difference (P＜0.05) with matched group, and dosage group 1.0mg/Kg compares significant difference with matched group more remarkable, P＜0.01); Show that peoniflorin has the splitted effect of the neural precursor of promotion.
Confirm through experimentation: the pharmaceutical composition toxic and side effects of prevention of the present invention and treatment depression is little, and effect is lasting, and is cheap.
Below in conjunction with the specific embodiment, introduce in detail peoniflorin of the present invention prevention and treatment aspect the depression application and contain the prevention of peoniflorin composition and the pharmaceutical composition of treatment depression.
Description of drawings
Fig. 1 horizontal anomalous movement is apart from block diagram (spacious experiment, vertical coordinate are the whole action distance of animal);
The non-swimming time block diagram (administration detected after 7 days) of Fig. 2 forced swimming experiment;
The non-swimming time block diagram of Fig. 3 forced swimming experiment (administration continued to raise 28 backs in 7 days and detects);
Fig. 4 food-intake block diagram (new environment feed suppresses experiment, and vertical coordinate is a food intake);
Block diagram incubation period of Fig. 5 feed (new environment feed suppresses experiment, and vertical coordinate is an eating time);
Fig. 6 horizontal movement is apart from block diagram (spacious experiment, vertical coordinate is the grid quantity of animal walking);
Fig. 7 cleannes block diagram (spacious experiment, vertical coordinate are that the animal cleaning that stands is modified the number of times of oneself);
Fig. 8 mouse brain SGZ district Brdu positive cell number.Wherein, A is a normal saline group mice ventricles of the brain other district Brdu positive cell displaing micro photo figure, B is peoniflorin (0.5mg/kg) the group mice ventricles of the brain other district Brdu positive cell displaing micro photo figure, C is peoniflorin (1.0mg/kg) the group mice ventricles of the brain other district Brdu positive cell displaing micro photo figure, and D is the mice ventricles of the brain other district Brdu positive cell number statistics block diagram of experimental group animal.
The specific embodiment
The present invention's a kind of natural active matter peoniflorin that extraction separation goes out from the root of Paeoniaceae plant peony and Paeonia suffruticosa can be applied in treatment depression medicine.
One, the separation of effective ingredient peoniflorin is purified
Utilize chemical method to be raw material from the root of Radix Paeoniae and Paeonia suffruticosa, preparation peoniflorin process is as follows:
The root of Radix Paeoniae or Paeonia suffruticosa, pulverize medical material, alcohol reflux with 70%, concentrating under reduced pressure, get dry extract, extractum adds water and fully dissolves, and crosses macroporous adsorptive resins, difference water, 20% ethanol elution, collect 20% ethanol elution, concentrating under reduced pressure gets extractum, through silica gel column chromatography separate the peoniflorin monomeric compound.(Hu Haiwei, macroporous adsorbent resin are used for the exploration of total paeony glycoside separation method for Jiang Huanrong, Pei Xuhong, Chinese patent medicine 1999,21 (12))
Two, drug effect and pharmacological action experiment
1, forced swimming experiment (FST): Porsolt equals to propose in 1977 the forced swimming model, find that different medicines is different to the change of forced swimming dead time in the FST test, antidepressants can effectively reduce the dead time, and this model is the effective method the most of screening antidepressants.Make animal be forced in the space swimming of a limitation, they are at first struggled and make an attempt at escaping, and just are in a kind of motionless state after through great efforts, and this motionless state is considered to the behavior despair, is a kind of desperate state that is similar to depression.The depth of water in the glass jar is the key factor that influences the rat forced swimming, and depth of water standard is the experimental mouse hind leg to be stretched can just contact cylinder bottom but be not enough to body support, and at the body weight of rat, the depth of water of this test and Selection is 40cm.Concrete steps are: trial test in the 1st day, and with the single uncovered clear glass cylinder (the high 50cm of cylinder, depth of water 40cm in the diameter 18cm, cylinder, water temperature 23-25 ℃) of putting into of experimental mouse, experimental mouse is taken out after putting into water 15min, and cage is put in 32 ℃ of oven dry.Trial test finishes back 24h, again with the single open glass cylinder of putting into of experimental mouse, measures the time of trip motionless (Immobility) in the 5min, with this index as the medicine antidepressant effect.Standard is the little health of curling up of experimental mouse, is floating state, surfaces in the nostril.Force the experimental model of experimental mouse swimming test for classical screening antidepressant drug, effectively antidepressant drug can make the dead time of experimental mouse swimming shorten.
Spacious experiment (open field): place high 50cm, length of side 100cm, periphery and bottom surface to be the square spacious field of black animal, illuminance is 60lux, indoor sound insulation.The observer in the behavior laboratory with the behavior performance of 3min before camera system record animal is in spacious, comprise horizontal anomalous movement apart from (TotleDistance), axial number of times, modify, probe into, dull and feces volume.Wherein the horizontal anomalous movement distance obtains data with probing into by the behavior tracking analytical system, and upright, grooming behavior is the number of times that takes place according to behavior video camera statistics.Determine that by spacious experiment the motor capacity of laboratory animal does not have significant difference.
Laboratory animal: SPF level bull C57 mice (18 ± 2 gram) is provided by Nanfang Medical Univ's Experimental Animal Center, the drinking-water of freely ingesting, and being raised in 12 hours is the environment (at 7 o'clock in the morning turned off the light) of a circulation light and shade conversion.Animal is divided into 6 groups at random, 10 every group.Raise beginning intraperitoneal injection of saline, peoniflorin, fluorine Luo Xiting and imipramine on the 7th from each treated animal, once a day, continuous 7 days, carry out the forced swimming experiment, detect the short-term antidepressant effect; Laboratory animal continues to raise 28 days, carries out the forced swimming experiment again, detects whether have long-term antidepressant effect.
Experimental result: the index result of horizontal anomalous movement distance shows that as shown in Figure 1, the physical quality of each laboratory animal group does not have significant difference in the experiment of spacious field; In the experiment of mice forced swimming, find: as shown in Figure 2, when administration detected in 7 days, peoniflorin can significantly shorten the time of motionless (immobility), and be dose dependent, compare with the antidepressants that fluorine Luo Xiting, imipramine etc. are existing, the peoniflorin antidepressant effect is best, at peoniflorin dosage very evident difference (P＜0.05) is arranged during for 0.5mg/kg, and when the peoniflorin administration concentration is 1mg/kg, can reduce the non-swimming time (P＜0.01) of rat by highly significant.We also observe the dead time that haloperidol can not shorten mice simultaneously, show that this experimentation has good repeatability.As shown in Figure 3, particularly find treatment 7 days, detected animal behavior again in 28 days after the drug withdrawal to find that peoniflorin still can shorten the dead time of mice, and effect is better during than 7 days, and be that the dose effect of 1mg/kg is best with the administration concentration.Fluorine Luo Xiting on the same group can not shorten the dead time of mice, though and imipramine can shorten the dead time of mice, its effect shows that obviously than 7 day time difference the antidepressant effect of peoniflorin is more lasting.
2, chronic mild Unpredictability depression model (CUS): according to the method for having set up, through open field test and the close animal of new environment feed experimental selection score, random packet, the lonely raising.Adopt folder tail (1min), braking (6h), electric shock vola (current intensity 1mA at random, 10s, 20 times), (4 ℃ of frozen water swimming, 5min), heat stress is (45 ℃, 5min), fasting (24h), prohibit water (24h), stroboscopic illumination (120 times/min, 1 night), white noise (4h) stimulates, and gives a kind of stimulation every day, modeling success and carry out open field test and behavioristics such as new environment feed is detected after continuous 21 days.
The proof box that the even high wood of 2cm in shop is cut at the bottom of new environment feed inhibition experiment (NSF): length of side 50cm, the high 40cm case, central authorities' placement sugar pill or morse are on blank sheet of paper at the bottom of the case.Rat fasting 24h before the test, amplify in the Mus cartonning from any case angle during test, observe 6min, the activity of record mice by camera system, count technology with the lattice that mice walks in proof box, calculate simultaneously by putting into mice and take the time (latency) that sugar pill is taken food in one's arms to the mice forelimb.The activity of mice and the length of eating time have been reacted the depressed degree of mice.Animal is put back to the interior food consumption quantity of record 2min in the cage subsequently, to get rid of the influence of appetite difference to eating time.
Laboratory animal: SPF level bull C57 mice (18 ± 2 gram) is provided by Nanfang Medical Univ's Experimental Animal Center, the drinking-water of freely ingesting, being raised in 12 hours is the environment of a circulation light and shade conversion, start injection peoniflorin and fluorine Luo Xiting after 21 days raised in modeling, every day 1 time, to 35 end of day, continue raising and began to detect to 42 days.
Experimental result shows: negative control normal saline group, positive control fluorine Luo Xiting group and peoniflorin administration group, suppress in the experiment in new environment feed, before modeling (before CMS), after the modeling/administration before after (before treatment) and the administration food-intake of (after treatment) mice all do not have statistics appetite difference (as shown in Figure 4), the appetite difference that mice is described is to not influence of eating time; Suppress the incubation period (Fig. 5) that experiment detects the mice feed in new environment feed, the eating time of mice is respectively organized in discovery before modeling very short, and each group does not have significant difference, all there is not feed and after modeling, respectively organize mice in experimental period, the modeling success is described, experiment mice is obvious depressive state, in administration after 14 days, the eating time of the mice of normal saline group does not obviously improve, and peoniflorin and fluorine Luo Xiting administration group have obviously been accelerated the eating time (P＜0.05) of mice, have improved the depressive state of mice; In spacious experiment, detect horizontal movement distance (Fig. 6) and the cleannes (Fig. 7) of mice, the number of squares and the number of times that cleaning is modified oneself of walking of respectively organizing experiment mice before modeling is all very many, the illustrative experiment Mus is in good body ﹠ mind state, these two groups of data of respectively organizing mice after the modeling all obviously reduce, illustrate that mice has been in depressive state, and find after 14 days in administration, the state of normal saline group does not have significant change, and motor capacity and the cleannes of fluorine Luo Xiting and peoniflorin administration group mice all obviously increase (P＜0.05), illustrate that fluorine Luo Xiting and peoniflorin have all obviously improved the depressed degree of laboratory animal.
3. the brain neuron of growing up is regenerated: behind the experiment mice intraperitoneal injection of drugs, give the Brdu50mg/kg lumbar injection simultaneously, give Animal Anesthesia behind the 24h, with buffered formalin infusion liquid (mixed liquor of 0.1MPB, 4%HCHO, PH=7.2), after aortic perfusion is fixing, get brain, make the crown frozen section of continuous brain (10-30um), immunohistochemical staining.With the anti-Brdu antibody test ventricles of the brain other district (SGZ district) Brdu positive cell and counting, 400X is record Brdu positive cell number down, and relatively each processed group promotes the effect of neural precursor propagation.
Laboratory animal: SPF level bull C57 mice (18 ± 2 gram) is provided by Nanfang Medical Univ's Experimental Animal Center, the drinking-water of freely ingesting, being raised in 12 hours is the environment of a circulation light and shade conversion, raise after 3 days, carry out the injection of medicine and Brdu antibody at 8 in the morning, pour at 8 in morning next day fixing, get brain, finish the value-added detection of cranial nerve precursor of growing up.
Experimental result: peoniflorin single intraperitoneal injection solution (0.1ml) dosage is 0.5mg/kg and 1.0mg/kg, with the normal saline feminine gender is matched group, the result shows (as Fig. 8), peoniflorin significantly increases the ventricles of the brain other district Brdu positive cell number, wherein dosage 0.5mg/Kg has compared remarkable significant difference (P＜0.05) with matched group, dosage group 1.0mg/Kg compares significant difference with matched group more remarkable, P＜0.01); Show that peoniflorin has the splitted effect of the neural precursor of promotion.
Experimental results show that more than peoniflorin has tangible antidepressant effect, thereby, can be used for the preparation prevention and treat antidepressant medicine.
The pharmaceutical composition that contains peoniflorin as active component and conventional medicine excipient or adjuvant provided by the invention contains the peoniflorin of 0.1-50% weight usually.
Pharmaceutical composition of the present invention can prepare according to methods known in the art.When being used for this purpose, if desired, active component and one or more solids or liquid medicine excipient and/or adjuvant can be combined, make and can be used as suitable administration form or the dosage form that people's medicine uses.
Drug regimen of the present invention can the unit dosage form administration, and route of administration can be intestinal or non-intestinal, as oral, muscle, subcutaneous, nasal cavity, oral mucosa, skin, peritoneum or rectum etc.
The route of administration of pharmaceutical composition of the present invention can be drug administration by injection.Injection comprises intravenous injection, intramuscular injection, subcutaneous injection, intradermal injection and acupoint injection therapy etc.
Form of administration can be liquid dosage form, solid dosage forms.As liquid dosage form can be solution class, colloidal type, particulate formulations, emulsion dosage form, mixed suspension form.Other dosage forms are tablet, capsule, drop pill, aerosol, pill, powder, solution, suspensoid, Emulsion, granule, suppository, lyophilized injectable powder etc. for example.
Compositions of the present invention can be made ordinary preparation, also can be slow releasing preparation, controlled release preparation, targeting preparation and various particulate delivery system.
For the unit form of administration is made tablet, can be extensive use of various carrier well known in the art.Example about carrier is, as diluent and absorbent: starch, dextrin, calcium sulfate, lactose, mannitol, sucrose, sodium chloride, glucose, carbamide, calcium carbonate, kaolin, microcrystalline Cellulose, aluminium silicate etc.; Wetting agent and binding agent: water, glycerol, Polyethylene Glycol, ethanol, propanol, starch slurry, dextrin, syrup, Mel, glucose solution, mucialga of arabic gummy, gelatine size, sodium carboxymethyl cellulose, lac, methylcellulose, potassium phosphate, polyvinylpyrrolidone etc.; Disintegrating agent, for example dry starch, alginate, agar powder, laminaran, sodium bicarbonate and citric acid, calcium carbonate, polyoxyethylene sorbitol fatty acid ester, dodecyl sodium sulfate, methylcellulose, ethyl cellulose etc.; The disintegrate inhibitor is as sucrose, glyceryl tristearate, cocoa butter, ammonification wet goods; Absorption enhancer, for example quaternary ammonium salt, sodium lauryl sulphate etc.; Lubricant, for example Pulvis Talci, silicon dioxide, corn starch, stearate, boric acid, liquid paraffin, Polyethylene Glycol etc.; Tablet further can also be made coated tablet, for example sugar coated tablet, thin membrane coated tablet, ECT, or double-layer tablet and multilayer tablet.
Make pill for the administration unit, can be extensive use of various carrier well known in the art.Example about carrier is, for example diluent and absorbent are as glucose, lactose, starch, cocoa butter, hydrogenated vegetable oil, polyvinylpyrrolidone, Gelucire, Kaolin, Pulvis Talci etc.; Binding agent is as arabic gum, Tragacanth, gelatin, ethanol, Mel, liquid sugar, rice paste or batter etc.; Disintegrating agent is as agar powder, dry starch, alginate, dodecyl sodium sulfate, methylcellulose, ethyl cellulose etc.
For suppository is made in the administration unit, can be extensive use of various carrier well known in the art, for example the ester of Polyethylene Glycol, lecithin, cocoa butter, higher alcohol, higher alcohol, gelatin, semi-synthetic glyceride etc.
For suppository is made capsule, effective ingredient is mixed with above-mentioned various carriers, and the mixture that will obtain thus places hard gelatine capsule or soft capsule, also effective ingredient can be made microcapsule, be suspended in and form suspensoid in the aqueous medium, in the hard capsule of also can packing into or make injection and use.
For example compositions of the present invention is made injection preparation, as solution, suspensoid solution, Emulsion, lyophilized injectable powder, this preparation can be moisture or non-water, can contain acceptable carrier, diluent, binding agent, lubricant, antiseptic, surfactant or dispersant on a kind of and/or multiple pharmacodynamics, can be selected from water, ethanol, Polyethylene Glycol, 1 as diluent, the isooctadecanol of ammediol, ethoxylation, the isooctadecanol of polyoxyization, Polyoxyethylene Sorbitol Fatty Acid Esters etc.In addition, ooze injection, can in injection preparation, add proper amount of sodium chloride, glucose or glycerol, in addition, can also add conventional cosolvent, buffer agent, pH regulator agent etc. in order to prepare etc.These adjuvants are that this area is commonly used.
In addition, as needs, also can in pharmaceutical preparation, add coloring agent, antiseptic, spice, correctives, sweeting agent or other materials.
Medicine of the present invention can consider that with the dosage of compositions individual variation changes within the specific limits, for example to prevent or treat the character and the order of severity of disease, the sex of patient or animal, age, body weight, personality and individual reaction, route of administration, administration number of times etc., in general, the using dosage of Chinese materia medica composition of the present invention is well known to a person skilled in the art.
The above only is preferred embodiment of the present invention, and is in order to restriction the present invention, within the spirit and principles in the present invention not all, any modification of being done, is equal to replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (6)
1, the application of peoniflorin in the medicine of preparation prevention and treatment depression.
2, the pharmaceutical composition of a kind of prevention and treatment depression, it comprises the peoniflorin of effective dose, and pharmaceutically acceptable carrier.
3, pharmaceutical composition as claimed in claim 2 is characterized in that, described pharmaceutical composition contains the peoniflorin of 0.1-50% weight.
4, pharmaceutical composition as claimed in claim 2 is characterized in that, the dosage form of described pharmaceutical composition is liquid dosage form or solid dosage forms.
5, pharmaceutical composition as claimed in claim 4 is characterized in that, described liquid dosage form is injection, solution, suspensoid, Emulsion, aerosol.
6, pharmaceutical composition as claimed in claim 4 is characterized in that, described solid dosage forms is tablet, capsule, pill, injectable powder, slow releasing preparation and various particulate delivery system.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011047576A1 (en) | 2009-10-20 | 2011-04-28 | Zhang Zuoguang | Use of albiflorin for anti-depression |
| CN103180334A (en) * | 2010-11-10 | 2013-06-26 | 张作光 | Method for preparing albiflorin and paeoniflorin |
| WO2013170637A1 (en) * | 2012-05-15 | 2013-11-21 | 北京京朋汇药业研究发展有限公司 | Application of paeoniflorin compound in preparation of antitumor drug |
| CN104666323A (en) * | 2013-11-27 | 2015-06-03 | 周亚伟 | Novel use of paeoniflorin or its derivative or salt |
| CN107308177A (en) * | 2017-07-19 | 2017-11-03 | 辽宁华润本溪三药有限公司 | A kind of pharmaceutical composition of antalgic and inflammation relieving and preparation method thereof and purposes |
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2008
- 2008-10-24 CN CNA2008102186245A patent/CN101385736A/en active Pending
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011047576A1 (en) | 2009-10-20 | 2011-04-28 | Zhang Zuoguang | Use of albiflorin for anti-depression |
| US9023817B2 (en) | 2009-10-20 | 2015-05-05 | Zuoguang Zhang | Use of albiflorin for anti-depression |
| CN103180334A (en) * | 2010-11-10 | 2013-06-26 | 张作光 | Method for preparing albiflorin and paeoniflorin |
| EP2650301A1 (en) * | 2010-11-10 | 2013-10-16 | Zuoguang Zhang | Method for preparing albiflorin and paeoniflorin |
| EP2650301A4 (en) * | 2010-11-10 | 2014-04-23 | Zuoguang Zhang | Method for preparing albiflorin and paeoniflorin |
| US9453041B2 (en) | 2010-11-10 | 2016-09-27 | Zuoguang Zhang | Method for preparing albiflorin and paeoniflorin |
| WO2013170637A1 (en) * | 2012-05-15 | 2013-11-21 | 北京京朋汇药业研究发展有限公司 | Application of paeoniflorin compound in preparation of antitumor drug |
| CN103417561A (en) * | 2012-05-15 | 2013-12-04 | 北京京朋汇药业研究发展有限公司 | Application of paeoniflorin compound in preparation of anti-tumor drug |
| CN103417561B (en) * | 2012-05-15 | 2015-10-28 | 北京京朋汇药业研究发展有限公司 | Paeoniflorin compound is preparing the purposes in antitumor drug |
| CN104666323A (en) * | 2013-11-27 | 2015-06-03 | 周亚伟 | Novel use of paeoniflorin or its derivative or salt |
| CN107308177A (en) * | 2017-07-19 | 2017-11-03 | 辽宁华润本溪三药有限公司 | A kind of pharmaceutical composition of antalgic and inflammation relieving and preparation method thereof and purposes |
| CN107308177B (en) * | 2017-07-19 | 2022-05-17 | 辽宁华润本溪三药有限公司 | Analgesic and anti-inflammatory pharmaceutical composition and preparation method and application thereof |
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